This invention relates to a method of intracorporeal iontophoretic treatment of body cavities or hollow organs. While in the following disclosure specific reference will be made to a preferred embodiment of the invention relating to the treatment of the bladder or prostatic urethra, it is to be understood that the invention is not limited to such treatments but equally applies to the treatment of other body organs meeting the conditions set forth hereinbelow, such as for example vagina.
Iontophoresis is most frequently defined as "the introduction, by means of an electric current, of ions of soluble salts into the tissues of the body for therapeutic purposes" (Dorland's Illustrated Medical Dictionary). The technique of iontophoresis has been in clinical use for more than a century and a great number of drugs have been administered by this method. Some, but by no means all, of the drugs include salts of penicillin, gentamycin, salicylates, fluoride, dexamethasone, hydrocortisone lidocaine, cocaine, morphine and doxorubicin.
By far the most common target site for iontophoretic treatments has been the skin, but the literature also reports a substantial number of treatments directed into the ears, the eyes, the tissues lining the mouth and the teeth. Reports of iontophoretic treatments within bodily cavities, other than the mouth, are very sparse.
In 1983 Davis et al obtained a U.S. Pat. No. 4,411,648, for the purpose of iontophoresing heavy metal ions, such as copper and silver, into the bladder cavity in order to prevent infection. Davis et al described the insertion of both the anode and the cathode into the bladder cavity in order to sterilize volumes of urine within the bladder cavity by means of heavy metal ions derived from the electrode materials themselves.
In chapter 97 of "FOLIA VETENNAVIA" 31, 1 (1987) there is described the treatment of colo-rectal cancers by iontophoresis of the drug, 5-fluorouracil, into the tumor sites using a double balloon catheter. More recently two German patent applications filed in the name of Thiel et al (DE 3809814 and DE 3844518), described iontophoretic delivery of Proflavin and various cogeners into the bladder wall for treatment of bladder cancers. The intravesical volume of drug used was large (200 ml), the currents used were very large (50 m A) and, except for an insulated urethral section and tip, the active electrode within the bladder was an unshielded conductive rod. Although various adjuvants were added to enhance the permeability of the bladder wall, no attempts were made to increase the electrochemical efficiency of drug delivery.
In spite of its inherent attractions iontophoresis has never attained widespread use in therapy probably because of some fundamental electrochemical problems which may be summarized here below.
Theoretically, the quantity (m) of drug (D) delivered by iontophoresis is proportional to the applied current (I) and its time of application: EQU m D.apprxeq.I.t.
Yet it has been shown unequivocally that, with iontophoretic administration of many drugs, the rate of drug delivery progressively diminishes with time. The main reason for this deterioration in performance of the iontophoretic system is associated with the transfer of electrical charge at the electrode (solid) - drug solution interface. For current to flow, electrical charge (electrons) must be transferred across this region. The electrons are derived either from dissolution of the electrode material and/or hydrolysis of water, at the anodic surface. For example: EQU Ag.fwdarw.Ag.sup.+ +e.sup.- EQU 2H.sub.2 O.fwdarw.4H.sup.+ +4e.sup.- +O.sub.2 .uparw.
In either case, electrons are provided and unwanted competitive ions (Ag.sup.+, H.sup.+) are generated.
At the cathode, electrons travel from the electrode into the drug solution, either as negatively charged ions or are again involved in the hydrolysis of water: EQU Ag/AgCl+e.sup.- --.fwdarw.Cl.sup.- EQU 2H.sub.2 O+2e.sup.- --.fwdarw.H.sub.2 .uparw.+2OH.sup.-
In order to overcome the disadvantages, and in particular the reduced efficiency of iontophoretic processes due to the accumulation in the iontophoretic environment of the competitive ions originated by the electrodes or by the hydrolysis of water, it has been proposed (e.g. in U.S. Pat. Nos. 4,570,637 and 4,747,819) to coordinate the selection of the electrode material and that of the drug counterion so as to provide during the electrochemical process, ionic species interacting the one with the other so as to minimize or reduce the amount of water hydrolisis products in the iontophoretic process.
None of the prior art references however recognized or dealt with the problems arising in intracorporeal iontophoresis of body cavities where an ion-rich physiological fluid environment exists, and none of them taught how to overcome such problems.